Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Affiliated Women's Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Clin Respir J. 2024 May;18(5):e13755. doi: 10.1111/crj.13755.
Lung adenocarcinoma (LUAD) is one of the most invasive malignant tumor of the respiratory system. It is also the common pathological type leading to the death of LUAD. Maintaining the homeostasis of immune cells is an important way for anti-tumor immunotherapy. However, the biological significance of maintaining immune homeostasis and immune therapeutic effect has not been well studied.
We constructed a diagnostic and prognostic model for LUAD based on B and T cells homeostasis-related genes. Minimum absolute contraction and selection operator (LASSO) analysis and multivariate Cox regression are used to identify the prognostic gene signatures. Based on the overall survival time and survival status of LUAD patients, a 10-gene prognostic model composed of ABL1, BAK1, IKBKB, PPP2R3C, CCNB2, CORO1A, FADD, P2RX7, TNFSF14, and ZC3H8 was subsequently identified as prognostic markers from The Cancer Genome Atlas (TCGA)-LUAD to develop a prognostic signature. This study constructed a gene prognosis model based on gene expression profiles and corresponding survival information through survival analysis, as well as 1-year, 3-year, and 5-year ROC curve analysis. Enrichment analysis attempted to reveal the potential mechanism of action and molecular pathway of prognostic genes. The CIBERSORT algorithm calculated the infiltration degree of 22 immune cells in each sample and compared the difference of immune cell infiltration between high-risk group and low-risk group. At the cellular level, PCR and CKK8 experiments were used to verify the differences in the expression of the constructed 10-gene model and its effects on cell viability, respectively. The experimental results supported the significant biological significance and potential application value of the molecular model in the prognosis of lung cancer. Enrichment analyses showed that these genes were mainly related to lymphocyte homeostasis.
We identified a novel immune cell homeostasis prognostic signature. Targeting these immune cell homeostasis prognostic genes may be an alternative for LUAD treatment. The reliability of the prediction model was confirmed at bioinformatics level, cellular level, and gene level.
肺腺癌（LUAD）是呼吸系统最具侵袭性的恶性肿瘤之一，也是导致 LUAD 死亡的常见病理类型。维持免疫细胞的内稳态是抗肿瘤免疫治疗的重要途径。然而，维持免疫内稳态和免疫治疗效果的生物学意义尚未得到很好的研究。
我们构建了一个基于 B 和 T 细胞稳态相关基因的 LUAD 诊断和预后模型。最小绝对收缩和选择算子（LASSO）分析和多变量 Cox 回归用于鉴定预后基因特征。基于 LUAD 患者的总生存时间和生存状况，从癌症基因组图谱（TCGA）-LUAD 中确定了由 ABL1、BAK1、IKBKB、PPP2R3C、CCNB2、CORO1A、FADD、P2RX7、TNFSF14 和 ZC3H8 组成的 10 个基因预后模型作为预后标志物，以开发预后模型。本研究通过生存分析以及 1 年、3 年和 5 年 ROC 曲线分析，基于基因表达谱和相应的生存信息构建基因预后模型。富集分析试图揭示预后基因的潜在作用机制和分子途径。CIBERSORT 算法计算每个样本中 22 种免疫细胞的浸润程度，并比较高风险组和低风险组之间免疫细胞浸润的差异。在细胞水平上，PCR 和 CKK8 实验分别用于验证构建的 10 个基因模型的表达差异及其对细胞活力的影响。实验结果支持该分子模型在肺癌预后中的显著生物学意义和潜在应用价值。富集分析表明，这些基因主要与淋巴细胞内稳态有关。
我们鉴定了一个新的免疫细胞内稳态预后标志。针对这些免疫细胞内稳态预后基因可能是 LUAD 治疗的一种替代方法。在生物信息学水平、细胞水平和基因水平上验证了预测模型的可靠性。
